The transport and biochemical transformations of the iodinated X-ray contrast medium (ICM) iomeprol were studied at the stream/groundwater interface. During a one-month field experiment piezometric pressure heads, temperatures, and concentrations of redox-sensitive species, iomeprol and 15 of its transformation products (TPs) were collected in stream- and groundwater. The data set was analyzed and transformation processes and rates identified by comparing conservative and reactive transport simulations. ICM and TP transformations were simulated as a cometabolic process during organic carbon degradation. Using iomeprol/TPs ratios as calibration constrain mitigated the uncertainties associated with the high variability of the ICM wastewater discharge into the investigated stream. The study provides evidence that biodegradation of ICM occurs at the field-scale also for predominantly denitrifying conditions. Under these anaerobically dominated field conditions shortest simulated half-life (21 days) was in the same range as previously reported laboratory-determined half-lives for aerobic conditions.